Public Release Type:
Journal
Publication Year: 2014
Authors:
Brahmania M,
Brouwer WP,
Feld J,
Hepatitis B Research Network,
Janssen H,
Kim WR,
Perrillo R,
Wong D
Studies:
Hepatitis B Research Network
Background and Aims: Flares in chronic hepatitis B (CHB) are a recognized phenomenon. We aimed to determine the incidence and predictors of flares in untreated CHB. Methods: Prospective (February 2011–current), multicenter, cohort study of adult CHB participants. Flares were pre-defined as ALT >10×ULN. Incidence, and differences in incidence, of flares was estimated with Kaplan–Meier method and with hazard ratios (HR) using Cox regression models. Results: Our cohort included 1745 participants, 1219 met eligibility. Mean age was 43 years (range: 18–80), 51% male, 73% Asian, 23% HBeAg(+) and 3.0% had advanced fibrosis (FIB-4 >3.25). Mean ALT, HBVDNA, and quantitative HBsAg levels were 2.0×ULN, 4.2 log10 (IU/ml), 3.2 log10 (IU/ml), respectively. Median follow up was 494 days (range: 1–992). 43 participants (1-year incidence: 3.8%) experienced a flare with median time to flare of 182 days. In contrast to non-flare participants, the flare population was younger (38.1 vs. 43.5; p = 0.006), HBeAg(+) (70.0% vs. 23.0%; p ≤ 0.0001), and immune active (48.8%; p < 0.0001). They also had higher baseline ALT (4.6 vs. 1.9×ULN; p = 0.002), HBVDNA (6.8 vs. 4.1 log10 (IU/ml); p < 0.0001), and quantitative HBsAg levels (3.9 vs. 3.2 log10 (IU/ml); p = 0.003). None of the 31 flares with a documented resolution led to hepatic decompensation. In multivariate analysis, significant factors associated with flares included male gender (HR 2.66; 95% CI: 1.34–5.26; p = 0.005), higher baseline ALT (HR 1.10; 95% CI: 1.06–1.15; p < 0.0001) and HBVDNA levels (HR 1.31; 95% CI: 1.07–1.61, p = 0.01). Conclusions: Male gender, HBeAg(+), high baseline levels of ALT and HBVDNA were all independently associated with higher risk of experiencing flares.